Article
Biochemistry & Molecular Biology
Yuan-Ren Cheng, Chih-Hung Chi, Cheng-Han Lee, Shing-Hong Lin, Ming-Yuan Min, Chih-Cheng Chen
Summary: The physiological response of proprioceptors to fatigue- and muscle-acidosis-related disturbances is still unclear. The effect of mild acidosis on the mechanosensitivity of dorsal root ganglia (DRG) neurons was investigated, revealing that acidification had an inhibitory effect on mechanosensitive currents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Eugen V. Khomula, Dioneia Araldi, Ivan J. M. Bonet, Jon D. Levine
Summary: Clinical mu-opioid receptor agonists induce maladaptive nociceptor neuroplasticity, resulting in pain chronification. This study established an in vivo and in vitro model to investigate the mechanisms underlying opioid-induced hyperalgesic priming in male rats.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Anesthesiology
Larissa Staurengo-Ferrari, Dioneia Araldi, Paul G. Green, Jon D. Levine
Summary: Stress can worsen cancer chemotherapy-induced peripheral neuropathy (CIPN) and play a role in the pain induced by oxaliplatin. Male rats with oxaliplatin-induced hyperalgesic priming showed prolonged hyperalgesia, which was attenuated in adrenalectomized rats. Neonatal handling prevented oxaliplatin-induced hyperalgesic priming. The hypothalamic-pituitary-adrenal and sympathoadrenal neuroendocrine stress axes were involved in oxaliplatin CIPN in rats.
Review
Pharmacology & Pharmacy
Li Chen, Dazhuo Shi, Ming Guo
Summary: PKC-delta and PKC-epsilon play crucial roles in protecting the myocardium during ischemia/reperfusion injury through their involvement in redox regulation, cell death, Ca2+ overload, and mitochondrial dysfunction.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Neurosciences
Sisi Wang, Junying Du, Danning Xi, Fangbing Shao, Mengting Qiu, Xiaomei Shao, Yi Liang, Boyi Liu, Xiaomin Jin, Jianqiao Fang, Junfan Fang
Summary: The study revealed that GABAAR plays a key role in the transition from acute to chronic pain, and electroacupuncture can increase the mechanical pain thresholds of hyperalgesic priming model mammals while upregulating GABAAR expression and inhibiting PKC epsilon activation in the DRG.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Anesthesiology
Caroline M. Kopruszinski, Moe Watanabe, Ashley L. Martinez, Luiz Henrique Moreira de Souza, David W. Dodick, Aubin Moutal, Volker Neugebauer, Frank Porreca, Edita Navratilova
Summary: Repeated stress can cause hyperalgesic priming, and the underlying mechanisms are not fully understood. This study investigated the effects of repeated administration of kappa opioid receptor (KOR) agonists and the potential involvement of prolactin (PRL) and prolactin receptor (PRLR) isoforms in sensory neurons. The results showed that KOR agonists increased circulating PRL and induced allodynia, which resolved within 14 days. Hyperalgesic priming was observed in both sexes after KOR agonist administration, but downregulation of PRLR isoforms was observed only in female mice. The study suggests a PRL/PRLR dependence in female nociceptors, which may contribute to pain in stress-related pain disorders in females.
Article
Neurosciences
Sridevi Nagaraja, Shivendra G. Tewari, Jaques Reifman
Summary: In this study, a computational model was used to identify key proteins involved in the development of hyperalgesic priming in muscle nociceptors. Alterations in the expression of Kv1.1 and Nav1.7 were found to regulate neuronal hyperexcitability in primed mechanosensitive muscle nociceptors.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alexandra Marsillo, Lovena David, Bishoy Gerges, Daniel Kerr, Rodina Sadek, Vitaliy Lasiychuk, David Salame, Youstina Soliman, Silvia Menkes, Aheli Chatterjee, Andrew Mancuso, Probal Banerjee
Summary: FXS, caused by the non-expression of the Fmr1 gene, leads to developmental disorders and abnormal behaviors mainly in males. Activation of PKCε has shown to correct abnormal behaviors in FXS mice during brain development and adulthood.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Endocrinology & Metabolism
Rafael C. Gaspar, Kun Lyu, Brandon T. Hubbard, Brooks P. Leitner, Panu K. Luukkonen, Sandro M. Hirabara, Ikki Sakuma, Ali Nasiri, Dongyan Zhang, Mario Kahn, Gary W. Cline, Jose Rodrigo Pauli, Rachel J. Perry, Kitt F. Petersen, Gerald I. Shulman
Summary: This study found that regular aerobic exercise can prevent the increase of muscle fat content, as well as reduce the content of sn-1,2-diacylglycerols (DAGs) in the cell membrane and the activation of protein kinase C (PKC), thus maintaining muscle insulin sensitivity.
Article
Biochemistry & Molecular Biology
Anibal Garza Carbajal, Andrea Ebersberger, Alina Thiel, Luiz Ferrari, Jeremy Acuna, Stephanie Brosig, Joerg Isensee, Katharina Moeller, Maike Siobal, Stefan Rose-John, Jon Levine, Hans-Georg Schaible, Tim Hucho
Summary: Hyperalgesic priming is characterized by enhanced nociceptor sensitization by pronociceptive mediators, with PGE(2) as a prototypical example. In this study, the cytokine OncostatinM was identified as an inducer of priming through a novel mechanism involving cAMP/PKA to ERK signaling. This finding sheds light on the complex cellular mechanisms underlying the transition to chronic pain.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rebecca Piccarducci, Chiara Giacomelli, Maria Sofia Bertilacchi, Andrea Benito-Martinez, Nicoletta Di Giorgi, Simona Daniele, Giovanni Signore, Silvia Rocchiccioli, Marcal Vilar, Laura Marchetti, Claudia Martini
Summary: The ApoE epsilon 4 polymorphic variant is a major risk factor for Alzheimer's Disease (AD) due to its effects on cholesterol metabolism and cholinergic pathway impairment. In this study, in vitro cholinergic neuron models were used to investigate the interplay between ApoE epsilon 4-related cholesterol metabolism dysregulation and cholinergic system degeneration. The results showed that ApoE epsilon 4 expression led to intracellular cholesterol accumulation and reduced acetylcholine synthesis, resulting in cholinergic pathway impairment and neuronal death.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Cell Biology
Anna E. D'Amico, Alexander C. Wong, Cheryl M. Zajd, Xuexin Zhang, Ananya Murali, Mohamed Trebak, Michelle R. Lennartz
Summary: The research revealed the essential role of PKC-ε in IgG-mediated phagocytosis, showing that its regulatory domain drives vesicles from the Golgi to the phagosome, while catalytic activity is required for their fusion. This study represents one of the first examples of a PKC requirement for vesicular trafficking and describes a novel function for a PKC regulatory domain.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Valentina La Cognata, Agata Grazia D'Amico, Grazia Maugeri, Giovanna Morello, Maria Guarnaccia, Benedetta Magri, Eleonora Aronica, Daniel L. Alkon, Velia D'Agata, Sebastiano Cavallaro
Summary: This study found a significant decrease in PKC epsilon expression in patients with amyotrophic lateral sclerosis (ALS), and the activation of PKC epsilon by Bryostatin-1 produced long-term survival in degenerating cells. These results suggest that PKC epsilon may play an important role in the pathophysiology of ALS and its pharmacological modulation could be a potential neuroprotective strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Athirah Hanim, Isa N. Mohamed, Rashidi M. P. Mohamed, Mohd Helmy Mokhtar, Suzana Makpol, Ruth Naomi, Hasnah Bahari, Haziq Kamal, Jaya Kumar
Summary: This study investigates the changes in mTORC2 and PKCε during different stages of ethanol exposure and finds that PKCε plays a role in alcohol use disorder-related behavioral alterations, especially in the amygdala. The study shows that PKC is phosphorylated at Ser729 before activation by the mTORC2 protein complex. The results suggest that PKCε protein expression is elevated in the amygdala during ethanol withdrawal and ethanol withdrawal followed by ethanol exposure.
Article
Neurosciences
Junying Du, Min Yi, Danning Xi, Sisi Wang, Boyi Liu, Xiaomei Shao, Yi Liang, Xiaofen He, Jianqiao Fang, Junfan Fang
Summary: Chronic pain is a common clinical syndrome that affects patients' quality of life. Neuroinflammatory responses play a role in pain transition and the development of chronic pain. In this study, a rat model was used to demonstrate that chemokine CXCL1 in the dorsal root ganglion is a key mediator of chronic pain and pain transition.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Anesthesiology
Der-Sheng Han, Cheng-Han Lee, Yih-Dar Shieh, Chu-Ting Chang, Min-Hsuan Li, Ya-Cherng Chu, Jaw-Lin Wang, Ke-Vin Chang, Shing-Hong Lin, Chih-Cheng Chen
Summary: The study found that dextrose injections can reduce mechanical hypersensitivity in a mouse model of fibromyalgia. The effectiveness of this treatment depends on the type of injectant, dose, and volume, but not on osmolarity. The antinociceptive effects are mediated through the activation of ASIC1a and substance P signaling pathways in muscle afferents. This study provides insights into the mechanism of action of dextrose prolotherapy in noninflammatory muscle pain and potential treatments for other chronic pain conditions.
Article
Anesthesiology
Wei-Hsiang Hsu, Der-Sheng Han, Wei-Chi Ku, Yen-Ming Chao, Chih-Cheng Chen, Yun-Lian Lin
Summary: This study identified potential biomarkers in fibromyalgia patients, which could differentiate between pain and soreness symptoms in FM patients. These biomarkers shed light on the underlying pathological mechanisms, offering insights for more effective diagnosis and therapy for FM.
EUROPEAN JOURNAL OF PAIN
(2022)
Review
Cell Biology
Yu-Chia Chuang, Chih-Cheng Chen
Summary: This article discusses mechanosensitive ion channels and their role in mechanotransduction. These channels are capable of converting different forms of mechanical force into electrical signals through variant gating models. Additionally, the article introduces another model for channel activation, which involves channels being opened through force tethering. The research also focuses on cytoskeletal proteins and the extracellular matrix involved in mechanotransduction.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jormay Lim, Ya-Cherng Chu, Hsiao-Hsin Tai, Andy Chien, Shao-Shiang Huang, Chih-Cheng Chen, Jaw-Lin Wang
Summary: This study quantified the optimal ultrasound dosage and long-term effects of transcranial ultrasound treatments for brain diseases. It was found that transcranial ultrasound promotes the increase of neural progenitors and this effect lasts at least a week, unaffected by auditory toxicity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Pei-Rung Wu, Shang-Yin Chiang, Robert Midence, Wen-Chao Kao, Chun-Lun Lai, I-Cheng Cheng, Shen-Ju Chou, Chih-Cheng Chen, Chih-Yang Huang, Ruey-Hwa Chen
Summary: Patients with mutations in the WDR4 gene exhibit cerebellar atrophy and gait phenotypes, but the underlying mechanisms have not been explored. This study reveals a crucial role of Wdr4 in cerebellar development. Deficiency of Wdr4 in granule neuron progenitors (GNPs) leads to reduced foliation, smaller external and internal granular layers, compromised Purkinje neuron organization, and smaller molecular layer, resulting in locomotion defects.
CELL DEATH & DISEASE
(2023)
Article
Health Care Sciences & Services
Hsiao-Yen Chiu, I-Wen Su, Yu-Wen Yu, Yi-Chen Chen, Chih-Cheng Chen, Jiann-Her Lin
Summary: This study aimed to investigate the prevalence and impacts of soreness or sng on the outcome of LSS. The results showed that soreness or sng had substantial clinical impacts on the outcome of LSS, indicating the need for independent assessment.
Article
Clinical Neurology
Der-Sheng Han, Cheng-Han Lee, Yih-Dar Shieh, Ke-Vin Chang, Shing-Hong Lin, Ya-Cherng Chu, Jaw-Lin Wang, Chih-Cheng Chen
Summary: Therapeutic ultrasound has analgesic effects against chronic muscle pain by activating ASIC3-containing channels and releasing substance P in muscle afferents.
Article
Rheumatology
Chih-Hsien Hung, Ming-Hsien Tsai, Po-Sheng Wang, Fu-Wen Liang, Chung-Yao Hsu, Kuo-Wei Lee, Yi-On Fong, Der-Sheng Han, Cheng-Han Lee, Chiou-Lian Lai, Chih-Cheng Chen
Summary: This study aimed to investigate the morbid soreness of fibromyalgia (FM), evaluate its therapeutic responses and probe its pathophysiology with metabolomics profiling. The results showed that soreness symptoms were prevalent in FM patients, with divergent phenotypes and metabolomic features between patients with mixed pain and soreness symptoms and those with pain dominant symptoms. Conventional treatment for FM did not ameliorate soreness severity, and metabolomics analyses suggested oxidative metabolism dysregulation and excessive oxidative stress in FM individuals.
Review
Physiology
Cheng-Han Lee, Chih-Cheng Chen
Summary: This review explores why proprioceptors, which are non-nociceptive, low-threshold mechanosensory neurons that monitor muscle contraction and body position, express several proton-sensing ion channels and receptors.
EXPERIMENTAL PHYSIOLOGY
(2023)
Review
Physiology
Yi-Chen Lin, Cheng-Han Lee, Jia-Ying Sung, Chih-Cheng Chen
Summary: Although ASICs are primarily responsible for sensing tissue acidosis, they are also involved in neurosensory mechanotransduction. However, their role as mechanically gated ion channels has not been confirmed using conventional mechanoclamp approaches. Instead, they are involved in the tether model of mechanotransduction, gated by tethering elements. New methods have been developed to investigate the roles of ASIC3 and ASIC1a in neurosensory mechanotransduction.
EXPERIMENTAL PHYSIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Chih-Hsien Hung, Yin Chin, Yi-On Fong, Cheng-Han Lee, Der-Sheng Han, Jiann-Her Lin, Wei-Hsin Sun, Chih-Cheng Chen
Summary: This review summarizes the roles of acid-sensing receptors in pain research and clinical pain diseases, highlighting their importance in pain perception and processing. It also proposes a new concept of sngception to address the specific somatosensory function of acid sensation. The findings from this review contribute to a better understanding of the acid-related pain pathogenesis and the potential therapeutic roles of acid-mediated antinociception.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Yuan-Ren Cheng, Chih-Hung Chi, Cheng-Han Lee, Shing-Hong Lin, Ming-Yuan Min, Chih-Cheng Chen
Summary: The physiological response of proprioceptors to fatigue- and muscle-acidosis-related disturbances is still unclear. The effect of mild acidosis on the mechanosensitivity of dorsal root ganglia (DRG) neurons was investigated, revealing that acidification had an inhibitory effect on mechanosensitive currents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)